We will extend previous studies defining the role of gastrointestinal mucosal barrier in control of intestinal antigen uptake. These studies include defining immuhologic (STgA) and non-immunologic (gstric barrier, mucus release, peristalsis, proteolysis) functions necessary to minimize antigen, bacteria and toxin penetration into the circulation. Having reported that intestinal immune complexes physically excluded antigens binding to enterocytes before pinocytosis and complexes enhance goblet cell mucus (GCM) release and pancreatic hydrolysis of proteins, we will characterize conditions of imune co plex formation (serum vs. secretory, antibody or antigen excess) for optimum antigen exclusion and define the specific mechanism for immune complex effect on GCM release, peristalsis, gastric emptying and protein digestion. Using Sprague-Dawley rats, mucosal and serum anti-BSA antibodies-125I-BSA complexes will be exposed to the intestine in vivo and in vitro. Attachment to the intestinal surface, movement through the intestine, breakdown to fragments and absorption to microvillus membranes of complexes will be compared with 125I-BSA antigen alone. The release mechanism of radiolabelled GCM (35S-GCM) and the protective properties of mucus against bacterial adherence, toxin attachment and antigen uptake will e studies. Using animal models for intestinal immaturity (newborn rabbits), intestinal inflammation and allergic reactions (Sprague-Dawley rats), the role of enhanced antigen uptake in IgG-mediated systemic protection or in IgG-complex immunopathologic responses will be assessed. Specific detail to hepatic clearance of IgG-specific and IgA-specific complexes will be made assuming that IgG complexes are cleared by hepatic Kupffer cells and IgA complexes by hepatocytes into the biliary tract. Finally clinical conditions (nflammatory bowel disease, viral gastroenteritis, cow's milk allergy, prematurity) will be studied by measuring circulating antigen, immune complexes and deposition of immune complexes in vital organs (intestine, liver, lung and kidney). This research may help define defects in the mucosal barrier to intestinal antigen which contributes to pathogenesis of diseases prolonged or extended by excessive uptake of antigens. This may help in clinical decisions as to nutrition in human infants and patients after a transient insult to the gut.